BRAIN DOES NOT UTILIZE LOW-DENSITY LIPOPROTEIN-CHOLESTEROL DURING FETAL AND NEONATAL DEVELOPMENT IN THE SHEEP

Several lines of evidence have suggested that central nervous system d evelopment and function depend upon a supply of cholesterol that comes from low density lipoproteins (LDL-C). These studies test this hypoth esis directly by measuring in vivo the uptake of LDL-C in nine regions of the central nervous system at five different stages of development in the fetal and neonatal sheep. The concentration of LDL-C in the pl asma decreased from 49 mg/dl in the fetus 90 days before birth (-90 da ys) to only 10 mg/dl at -13 days. By 17 days postnatal this value incr eased to nearly 60 mg/dl. Throughout the period of development between -90 days (very early fetus) and 17 days (late neonatal animal) the we ight of the brain increased 32-fold (from 2.3 to 73.6 g) and the conte nt of cholesterol rose 100-fold (from 8.6 to 876 mg), yet there was no detectable LDL-C uptake in any of nine areas of the central nervous s ystem at any stage of development (clearances of <2 mu l/h per g). Thi s was true even in the -90 day fetus prior to closure of the blood bra in barrier. In contrast, LDL-C clearance by the adrenal gland increase d dramatically (from 91 to 348 mu l/h per g) as it also did in the liv er (from 36 to 85 mu l/h per g) during fetal development. These studie s strongly suggest, therefore, that cholesterol carried in LDL plays l ittle or no role in the process of sterol acquisition during brain dev elopment or in cholesterol turnover in the mature central nervous syst em. Changes in circulating LDL-C concentration, therefore, should have no effect on brain function.